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Low Dose Azacitidine after Transplant in Preventing Recurrence in Patients with Myelodysplastic Syndromes or Acute Myeloid Leukemia in Remission

Trial Status: Active

This phase II trial studies the side effects and how well low dose azacitidine after transplant works in preventing cancer from coming back in patients with myelodysplastic syndromes or acute myeloid leukemia in remission. Drugs used in chemotherapy, such as azacitidine, work to stop the growth of cancer cells either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Inclusion Criteria

  • Patients who have undergone T-cell depleted allogeneic hematopoietic stem cell transplantation at Memorial Sloan-Kettering Cancer Center (MSKCC) for:
  • De novo myelodysplastic syndromes (MDS): International Prognostic Scoring System intermediate-1 (IPSS-1) with poor risk cytogenetics or higher IPSS
  • Acute myelogenous leukemia (AML) in first remission that required more than 1 cycle of treatment to achieve remission or with the following cytogenetic abnormalities: FLT3 mutation, deletion/monosomy of chromosome 5 or 7, MLL gene rearrangement, or more than or equal to 3 cytogenetics abnormalities; also patients in second or greater remission
  • Patients with secondary MDS/AML
  • Patients will be considered eligible for the study if after transplant they achieved hematologic (< 5% blasts) and cytogenetic remission
  • Patients will be eligible to enter the study between 60-120 days post-transplant
  • Karnofsky performance status >= 60% for patients > 16 years old (yo) and Lansky performance status >= 60% for patients =< 16 yo
  • Absolute neutrophil count (ANC) > 1000/uL not supported by transfusions
  • Hemoglobin (Hb) > 8 gr/dL not supported by transfusions
  • Platelets > 50,000/uL not supported by transfusions
  • Serum creatinine < 1.5 upper limit of normal (ULN)
  • < 3 x ULN alanine aminotransferase (ALT), unless there is congenital benign hyperbilirubinemia
  • < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia
  • Adequate cardiac function measured by left ventricular ejection fraction (LVEF) > 50%; if asymptomatic, pre-transplant echocardiogram is adequate; if symptomatic, echocardiogram needs to be repeated
  • Each patient must be willing to participate as a research subject and must sign an informed consent form
  • Patients who were treated with 5'-azacitidine without response prior to transplant would be eligible to participate on this protocol

Exclusion Criteria

  • Active uncontrolled bacteria, fungal or viral infection
  • Evidence of uncontrolled graft-versus-host disease
  • Pulmonary: new onset hypoxia
  • Known or suspected hypersensitivity to 5'-azacitidine or mannitol
  • Evidence of residual disease either by increased blasts count (> 5%) or persistence of previous known cytogenetics abnormalities
  • Peripheral blood neutrophil chimerism: less than 95% donor

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: ACTIVE
Contact: Roni Tamari
Phone: 212-639-5987
Middletown
Memorial Sloan Kettering Monmouth
Status: ACTIVE
Contact: Roni Tamari
Phone: 212-639-5987

New York

Commack
Memorial Sloan Kettering Commack
Status: ACTIVE
Contact: Roni Tamari
Phone: 212-639-5987
New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Roni Tamari
Phone: 212-639-5987
Uniondale
Memorial Sloan Kettering Nassau
Status: ACTIVE
Contact: Roni Tamari
Phone: 212-639-5987
West Harrison
Memorial Sloan Kettering Westchester
Status: ACTIVE
Contact: Roni Tamari
Phone: 212-639-5987

PRIMARY OBJECTIVES:

I. To evaluate whether maintenance treatment post transplant with 5-azacitidine (azacitidine) can reduce the relapse rate over the current standard of care for high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients.

SECONDARY OBJECTIVES:

I. To assess overall survival from the time of 5-azacitidine initiation.

II. To confirm the safety and tolerability of low dose 5'-azacitidine by measuring the frequency of transfusions, frequency of bleeding, frequency of serious infections, and use of filgrastim (G-CSF) support.

III. To evaluate graft function and myeloid and T-cell chimerism after administration of low dose 5'-azacitidine.

IV. To evaluate the incidence of acute and chronic graft versus host disease (GvHD) following the initiation of 5-azacitidine.

CORRELATIVE OBJECTIVES:

I. Correlate treatment with low dose 5’-azacitidine with gene specific methylation in the hematopoietic stem cell (HSC) compartment in cluster of differentiation (CD) 34 cells subpopulations.

II. Correlate treatment with low dose 5’-azacitidine with recurrence of cytogenetic abnormalities in the hematopoietic stem cell (HSC) compartment in CD34 cells subpopulations.

III. Correlate treatment with low dose 5’-azacitidine with normalization of myeloid progenitor frequencies known to be altered in MDS.

IV. Correlate treatment with low dose 5’-azacitidine with level of regulatory T cells (CD4+CD25-FoxP30).

OUTLINE:

Patients receive azacitidine subcutaneously (SC) on days 1-5. Treatment repeats every 28 days for up to 8-10 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 24 months.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Roni Tamari

  • Primary ID 13-192
  • Secondary IDs NCI-2014-00673
  • Clinicaltrials.gov ID NCT01995578